Lecture 1

Question 1

What is the most crucial building block of medical genetics?

Answer 1

The phenotype. All genetics questions start here.

Question 2

What is cytogenetics?

Answer 2

The examination of chromosomes for physical rearrangements

Question 3

What are the two type of rearrangements in chromosomes?

Answer 3

Germline and somatic

Question 4

What are the 3 major cytogenetics techniques?

Answer 4

• G banding (majority)
• fluorescent in situ hybridization (FISH)
• More recently, comparative genomic hybridisation (CGH)

Question 5

Describe the G banding Technique.

Answer 5

• It uses metaphases chromosomes
• Trypsin treatment strips off the histones (reveal DNA)
• stain with Giesma
• Binds to A-T sequence (chromatin dense and gene poor)

Question 6

What is R-banding?

Answer 6

The inverse of G-banding (gene rich, stain with chromomycin)

Question 7

What is a karyotype

Answer 7

The image and description of a chromosomal compliment

Question 8

What are you looking for from G-banding?

Answer 8

A visible karyotype. Large structural changes, as they can give insight into specific gene locations and specific diseases.

Question 9

What are translocations?

Answer 9

Exchange between non-homologous chromosomes

Question 10

What does the exchange of centric and acentric fragments cause?

Answer 10

Dicentric + acentric chromosomes. It is not stable in mitosis.

Question 11

What does the exchange of 2 acentric fragments cause?

Answer 11

Stable reciprocal translocation. Somewhat common in healthy humans.

Question 12

What does exchange in proximal short arms cause?

Answer 12

Stable Robertsonian Translocation, one chromosome is lost, one formed between attached chromosomes

Question 13

What happens in meiotic non-disjunction?

Answer 13

If it occurs at meiosis II and not I, one gamete has 24 chromosomes, one has 22. If it doesn’t occur at either meiosis both gametes are normal. If it occurs at meiosis I, 2 gametes will have 24, 2 will have 22

Question 14

Prevalence of down syndrome?

Answer 14

1:800/1000 live births

Question 15

What causes down syndrome?

Answer 15

Chromosomal non-disjunction

Question 16

Symptoms of Fragile X syndrome?

Answer 16

Moderate to severe mental retardation.
Macroorchidism (Large testicles)
Distinct facial features, long face, large ears, prominent jaw
In some cases Autism/Aspergers ADHD

Question 17

What is the prevalence of Fragile X syndrome?

Answer 17

Half of X-linked mental retardation cases. Second most common cause of mental impairment after trisomy 21.
1:4000 in boys, 1:8000 in girls (Despite being an X-linked condition)

Question 18

Pathology of Fragile X?

Answer 18

• Caused by unstable expansion of (CGG)n repeat in FMR1 gene

- Abnormal methylation, which results in suppression of FMR1 transcription and decreased protein levels in the brain

Question 19

What is the phenotype for Chronic Myeloid Leukemia (CML)?

Answer 19

• Cancer of the WBCs
• Up regulated growth of myeloid cells in bone marrow
• Anemia
• Increased susceptibility to infections
• Low platelet count
• Blast crisis (after additional mutations)

Question 20

What is the abnormality in CML and where is it seen?

Answer 20

On chromosome 22, known as the Philadelphia Chromosome, there is a translocation with chromosome 9. Likely due to homologous sections on both chromosomes.